What Causes Graves Disease? Key Triggers Explained

What is Graves Disease?

Graves’ disease is an autoimmune disorder that affects the thyroid gland, a butterfly-shaped gland in the neck. The thyroid gland produces two important hormones: triiodothyronine (T3) and thyroxine (T4). These hormones are responsible for regulating  metabolism, heart rate, temperature, body weight, menstrual cycles, and other bodily functions. People with Graves disease have too much thyroid hormone in their bodies, resulting in hyperthyroidism or overactive thyroid. 

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), about 1 in 100 people in the U.S. have Graves disease. It is the most common cause of hyperthyroidism (60 to 80% of cases of hyperthyroidism are due to Graves disease).

What is the Main Cause of Graves Disease?

The main cause of Graves’ disease is the body’s immune system not working properly. 

In healthy people, the pituitary gland in the brain controls thyroid hormone production by releasing a hormone called the thyroid-stimulating hormone (TSH). In people with Graves disease, the immune system produces antibodies called thyrotropin receptor antibodies (TRAb), also called thyroid-stimulating immunoglobulin (TSI). This antibody takes over the function of the pituitary gland and causes thyroid cells to make too much hormone. 

The increased thyroid hormone production results in Graves disease with symptoms of hyperthyroidism (overactive thyroid). 

Symptoms of Graves Disease

Because the thyroid hormone controls many important functions in the body, patients with Graves disease can have a wide range of hyperthyroidism symptoms throughout their body, including:

• Enlarged thyroid gland (goiter)

• Fatigue

• Mild tremor in the hands or fingers

• Heat sensitivity 

• Increased sweating 

• Warm, moist skin

• Weight loss despite a normal or increased appetite

• Menstrual cycle changes

• Erectile dysfunction (inability to get or keep an erection) 

• Decreased libido 

• Frequent bowel movements 

• Nervousness or irritability

• Bulging eyes (called Graves ophthalmopathy or thyroid eye disease)

• Thick, discolored skin on the feet and shins (called Graves dermopathy or pretibial myxedema)

• Palpitations (rapid and irregular heartbeat, especially in elderly people)

• Sleep difficulties

Why Does Graves Disease Develop? 

Autoimmune Reactions

As mentioned, Graves’ disease belongs to a group of disorders called autoimmune diseases. These diseases develop when the immune system attacks healthy cells and tissues in the body. 

Scientists believe a combination of genetic and environmental factors causes the immune system to make excess thyroid-stimulating immunoglobulins (TSI) (also called thyrotropin receptor antibodies or TRAb). TSI then binds to the thyroid-stimulating hormone receptor on the healthy thyroid cells, leading to the overproduction of thyroid hormones. 

People with Graves' disease are at an increased risk of developing other autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus (SLE), pernicious anemia, celiac disease, Addison disease, and vitiligo. They are also at risk of thyroid nodules and thyroid cancer. 

Genetic Predispositions 

Changes in certain genes are known risk factors for the development of Graves’ disease. A family of genes called the human leukocyte antigen (HLA) complex is implicated in this thyroid disease. These genes are responsible for helping the immune system differentiate between proteins that are naturally found in the body and invaders such as bacteria and viruses. In addition, genes that control immune function and thyroid function are associated with Graves disease. However, research suggests these genetic changes play a small role in the risk of developing symptoms of Graves disease.

Environmental Factors

Environmental or non-genetic factors can potentially trigger Graves' disease in high-risk individuals. Researchers have not identified the exact mechanism. Possible triggers include: 

• Infections (virus, bacteria)

• Sex hormone fluctuation, such as during pregnancy

• Too little or too much iodine in the body (iodine is essential for thyroid hormone production) 

• Smoking (smoking is a risk factor for developing eye problems which are present in 25% of people with Graves disease)

• Stress

• Certain medications

Note: Thyroid hormone replacement such as levothyroxine (Synthroid) is used to treat an underactive thyroid (hypothyroidism or too little thyroid hormone). Taking high doses of these medications can cause symptoms of hyperthyroidism. However, these symptoms are not due to Graves disease and are reversible. Learn more about the difference between an underactive thyroid and an overactive thyroid.

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Risk Factors and Demographics

• Family history: Many people who develop Graves' disease have a close relative with the condition. 

• Sex: Graves disease is more common in women than men. 

• Age: Graves' disease is frequently diagnosed between the ages of 30 and 60.

• Other autoimmune conditions: People with other autoimmune conditions are at a higher risk of developing Graves disease. 

• Smoking: Smoking affects the immune system and increases the risk of Graves disease as well as eye problems associated with the condition.

Middle-aged women who are smokers and have a family history of Graves disease and/or a history of other autoimmune disorders are at highest risk of developing Graves’ disease.

Graves' Flare-Ups

Flare-Up Triggers

Certain lifestyle habits and environmental triggers can make the symptoms of Graves disease worse and cause a flare-up, including:

• Smoking is a known risk factor for thyroid eye disease. If you have a diagnosis of Graves disease, quitting smoking can lower your risk of developing eye symptoms.

• Caffeine can make Graves disease symptoms such as anxiety, nervousness, palpitations, tremor, and frequent bowel movements worse.

• Stress can worsen symptoms such as palpitations, nervousness, and anxiety. 

• Medications: Over-the-counter thyroid supplements can worsen Graves symptoms. 

• Pregnancy can cause Graves to flare up due to hormonal changes.

• Contrast dye, which is used in many imaging studies, contains iodine, which can worsen symptoms in Graves disease patients.

What Does A Graves Flare-Up Feel Like?

A severe flare-up of Graves disease is called a thyroid storm, thyrotoxic crisis, or accelerated hyperthyroidism. This is a medical emergency and is more likely to happen in people with untreated or undertreated severe hyperthyroidism.

During a thyroid storm, there is a sudden and dramatic rise in thyroid hormone levels in the body. This causes symptoms such as fever, weakness, tremors, sweating, confusion, delirium, irregular heartbeat, low blood pressure, and coma. 

How is Graves Disease Diagnosed?

Doctors can make a diagnosis of Graves disease based on your symptoms, medical history, physical exam, blood tests (including autoantibody testing), thyroid scan, and a radioactive iodine uptake test.

Find out “What is a TSH Blood Test?”

Can Graves' Disease Be Cured?

There is no cure for Graves disease. However, treatments are available to manage the symptoms of Graves disease.

Treatment Options for Graves Disease

Radioactive iodine treatment

Radioactive iodine therapy involves taking radioactive iodine or radioiodine by mouth. Radioiodine therapy destroys thyroid cells and causes your thyroid gland to shrink over time. This leads to decreased thyroid hormone production over a period of several weeks to months. 

Antithyroid medicines

Prescription anti-thyroid medications, propylthiouracil and methimazole block excess hormone production by the thyroid gland. They can be used before or after radioiodine treatment. 

Beta-blockers

Beta blockers do not cause the thyroid gland to make less thyroid hormone, but they reduce the effects of the hormones on the body. They are used to treat Graves disease symptoms such as irregular heartbeat, rapid heartbeat, tremors, muscle weakness, irritability, anxiety, sweating, heat intolerance, and diarrhea. Examples include atenolol (Tenormin), propranolol (Inderal LA), nadolol (Corgard), and metoprolol (Toprol XL, Metoprolol).

Thyroid surgery

Surgical removal of the thyroid gland is called thyroidectomy. This surgery is sometimes done to treat Graves' disease. People who undergo thyroidectomy eventually develop hypothyroidism (underactive thyroid or not enough thyroid hormone) and need to take thyroid replacement lifelong.

Treatments for thyroid eye disease

Thyroid eye disease symptoms are treated using:

• Artificial tears

• Corticosteroids 

• Teprotumumab (Tepezza), a monoclonal antibody

• Eyeglass prisms to treat double vision 

• Orbital decompression surgery

• Orbital radiotherapy

Long-Term Management and Living With Graves' Disease

If you have had Graves disease and hyperthyroidism diagnosed, it is important to follow your doctor’s treatment plan. This is a chronic condition without a cure that requires long-term management. Taking your thyroid hormone medicine as prescribed will stop thyroid hormone production. In addition to stopping your thyroid gland from producing excess thyroid hormone, treatments for Graves’ disease can also reduce the effects of stored thyroid hormone on various organs in your body.

How Long Can Someone Live With Graves' Disease?

Graves disease does not affect how long you can live if you manage the condition well. However, without treatment, serious complications of Graves disease, such as thyroid storm and heart disease, can affect life expectancy.